PTH has both catabolic and anabolic properties, and under normal circumstances, PTH in PHPT is catabolic for bone at the cortical skeleton. Recently, evidence for a direct role of PTH on RANKL expression and osteoclastogenesis in vivo was obtained using mice lacking a distant transcriptional enhancer of the RANKL gene that confers responsiveness to PTH. These observations, supported by additional cross-sectional studies in human subjects make a compelling argument that the catabolic actions of PTH are mediated by RANKL-mediated bone resorption.